Glucocorticoid-resistant asthma: more than meets the eye

Reddy, Divya; Little, Frédéric F.

doi:10.3109/02770903.2013.831870

Cited by 20 publications

(15 citation statements)

References 62 publications

(67 reference statements)

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“…Smoking has been found to increase the risk of airway obstruction in adults who develop asthma after the age of 10 years [20]. This finding is relevant, since smoking is one of the risk factors that influence therapeutic response to corticosteroids, and is thus related to poor asthma control [21].…”

Section: Discussionmentioning

confidence: 82%

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Self-perceived Sleep Quality and Quantity in Adults With Asthma: Findings From the CosteAsma Study

Burgoa

Rejas

Ojeda

2016

J Investig Allergol Clin Immunol

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Background and Objective: Nocturnal asthma symptoms are associated with poor sleep quality, excessive daytime sleepiness, and poor daytime functioning. The aim of this study was to describe self-perceived sleep quality and quantity in asthmatic adults in a real-world setting according to different determinants of patient health status. Methods: A cross-sectional, observational, seasonal, multiwave survey was designed. Allergists nationwide were asked to consecutively survey adult asthmatics aged 18 to 65 years, evenly distributed by seasons and asthma severity (Global Initiative for Asthma criteria). Sleep quality and quantity were assessed using the self-administered Medical Outcomes Study (MOS) Sleep Scale. The Asthma Control Test was applied to ascertain the degree of asthma symptom control. Results: A total of 1098 individuals (58.7% females, 41.2 [13.6] years) were analyzed. Asthma severity was associated with poor sleep quality and quantity; patients with more severe disease scored higher on the MOS Sleep Scale (P<.001) and also reported significantly fewer daily average hours of sleep (0.3-0.5 hours, P<.001). Level of symptom control and asthma severity were both associated with poor sleep quality and quantity, with the following mean MOS sleep problem index scores: 25.3 (fully controlled asthma), 26.4 (controlled), 32.6 (partly controlled), and 44.6 (uncontrolled) (P<.001), and 48.4 (severe asthma), 39.0 (moderate), 32.6 (mild), and 26.5 (intermittent) (P<.001). Sex was significantly associated with the summary MOS sleep problem index. Conclusions: Sleep quality and quantity was significantly associated with poor health status in asthmatic patients. Guidelines should recommend asking about nocturnal asthma symptoms and encourage clinicians to take a global sleep history. Better control of nocturnal asthma symptoms could lead to improved sleep quality and a decrease in daytime sleep-related symptoms.

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Section: Discussionmentioning

confidence: 82%

“…It is recommended that the ACT should be taken at different times of the year. We classified degree of asthma control into 4 categories based on ACT scores [9]: uncontrolled asthma (≤15 points), partly controlled asthma (16)(17)(18)(19), controlled asthma (20)(21)(22)(23)(24), and fully controlled asthma (25 points).…”

Section: Data Collection and Measurementsmentioning

confidence: 99%

Self-perceived Sleep Quality and Quantity in Adults With Asthma: Findings From the CosteAsma Study

Burgoa

Rejas

Ojeda

2016

J Investig Allergol Clin Immunol

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“…Genetic studies for loci linked to susceptibility to asthma have identified candidates involved in immune function (e.g., innate immunity, immunoregulation, and T-cell differentiation), epithelial cell function (e.g., genes involved in epithelial biology and mucosal immunity), and genes involved in lung function and the remodeling of airways (6). Although it is well established that the development of asthma and asthmatic symptoms are dependent on an immune response, suppressing immune responses and antiinflammatory treatments only partially control symptoms, suggesting that cellular mechanisms outside the immune system add to the expression of this lung disease (3,7,8). Notably, a significant body of physiological data suggests that asthmatic symptoms may be significantly modulated by the nervous system (9, 10).…”

Section: Bronchospasms | Airway Inflammationmentioning

confidence: 99%

Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways

Tränkner

Hahne

Sugino

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

189

195

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Asthma is a common debilitating inflammatory lung disease affecting over 200 million people worldwide. Here, we investigated neurogenic components involved in asthmatic-like attacks using the ovalbumin-sensitized murine model of the disease, and identified a specific population of neurons that are required for airway hyperreactivity. We show that ablating or genetically silencing these neurons abolished the hyperreactive bronchoconstrictions, even in the presence of a fully developed lung inflammatory immune response. These neurons are found in the vagal ganglia and are characterized by the expression of the transient receptor potential vanilloid 1 (TRPV1) ion channel. However, the TRPV1 channel itself is not required for the asthmatic-like hyperreactive airway response. We also demonstrate that optogenetic stimulation of this population of TRP-expressing cells with channelrhodopsin dramatically exacerbates airway hyperreactivity of inflamed airways. Notably, these cells express the sphingosine-1-phosphate receptor 3 (S1PR3), and stimulation with a S1PR3 agonist efficiently induced broncho-constrictions, even in the absence of ovalbumin sensitization and inflammation. Our results show that the airway hyperreactivity phenotype can be physiologically dissociated from the immune component, and provide a platform for devising therapeutic approaches to asthma that target these pathways separately.bronchospasms | airway inflammation

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“…13, 14 It should be noted that steroid resistance frequently develops in patients. 15, 16, 17 Interestingly, in clinical investigations when MSCs are used to promote tissue repair in steroid-resistant patients, in whom inflammation continues, impressive results are often achieved. 5, 18 Unfortunately, the administration of MSCs has not been always successful.…”

mentioning

confidence: 99%

The interaction between mesenchymal stem cells and steroids during inflammation

Chen

Gan

et al. 2014

Cell Death Dis

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Mesenchymal stem cells (MSCs) are believed to exert their regenerative effects through differentiation and modulation of inflammatory responses. However, the relationship between the severity of inflammation and stem cell-mediated tissue repair has not been formally investigated. In this study, we applied different concentrations of dexamethasone (Dex) to anti-CD3-activated splenocyte cultured with or without MSCs. As expected, Dex exhibited a classical dose-dependent inhibition of T-cell proliferation. Surprisingly, although MSCs also blocked T-cell proliferation, the presence of Dex unexpectedly showed a dose-dependent reversion of T-cell proliferation. This effect of Dex was found to be exerted through interfering STAT1 phosphorylation-prompted expression of inducible nitric oxide synthase (iNOS). Interestingly, inflammation-induced chemokines in MSCs was unaffected. To test the role of inflammation severity in stem cell-mediated tissue repair, we employed mice with carbon tetrachloride-induced advanced liver fibrosis and found that although MSCs alone were effective, concurrent administration of Dex abrogated the therapeutic effects of MSCs on fibrin deposition, serum levels of bilirubin, albumin, and aminotransferases, as well as T-lymphocyte infiltration, especially IFN-γ+CD4+ and IL-17A+CD4+T cells. Likewise, iNOS−/− MSCs, which produce chemokines but not nitric oxide under inflammatory conditions, are ineffective in treating advanced liver fibrosis. Therefore, inflammation has a critical role in MSC-mediated tissue repair. In addition, concomitant application of MSCs with steroids should be avoided.

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Glucocorticoid-resistant asthma: more than meets the eye

Cited by 20 publications

References 62 publications

Self-perceived Sleep Quality and Quantity in Adults With Asthma: Findings From the CosteAsma Study

Self-perceived Sleep Quality and Quantity in Adults With Asthma: Findings From the CosteAsma Study

Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways

The interaction between mesenchymal stem cells and steroids during inflammation

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